WO1996031208A2 - Utilisation de composes de piperidine ou de pyrrolidine substitues pour le traitement de maladies modulees par un recepteur sigma - Google Patents
Utilisation de composes de piperidine ou de pyrrolidine substitues pour le traitement de maladies modulees par un recepteur sigma Download PDFInfo
- Publication number
- WO1996031208A2 WO1996031208A2 PCT/EP1996/001442 EP9601442W WO9631208A2 WO 1996031208 A2 WO1996031208 A2 WO 1996031208A2 EP 9601442 W EP9601442 W EP 9601442W WO 9631208 A2 WO9631208 A2 WO 9631208A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hydrogen
- use according
- treated
- phenyl
- disease
- Prior art date
Links
- 108010085082 sigma receptors Proteins 0.000 title abstract description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title description 3
- 150000003053 piperidines Chemical class 0.000 title description 2
- 150000003235 pyrrolidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 31
- 239000003814 drug Substances 0.000 claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 18
- -1 2-norbornen-5-yl Chemical group 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- QIHLUZAFSSMXHQ-UHFFFAOYSA-N budipine Chemical compound C1CN(C(C)(C)C)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 QIHLUZAFSSMXHQ-UHFFFAOYSA-N 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- YSXKPIUOCJLQIE-UHFFFAOYSA-N biperiden Chemical compound C1C(C=C2)CC2C1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 YSXKPIUOCJLQIE-UHFFFAOYSA-N 0.000 claims description 6
- 229960003003 biperiden Drugs 0.000 claims description 6
- OGAKLTJNUQRZJU-UHFFFAOYSA-N diphenidol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)CCCN1CCCCC1 OGAKLTJNUQRZJU-UHFFFAOYSA-N 0.000 claims description 6
- 229960003520 diphenidol Drugs 0.000 claims description 6
- RQXCLMGKHJWMOA-UHFFFAOYSA-N pridinol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 RQXCLMGKHJWMOA-UHFFFAOYSA-N 0.000 claims description 6
- 229960003195 pridinol Drugs 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- 208000028017 Psychotic disease Diseases 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- HWSIZQMXQQXDNZ-UHFFFAOYSA-N 1-(2,3,4,5,6,7-hexahydro-1h-tricyclo[2.2.1.0^{2,6}]heptan-3-yl)-1-phenyl-3-piperidin-1-ylpropan-1-ol;hydrochloride Chemical compound Cl.C1C2C3C2CC1C3C(C=1C=CC=CC=1)(O)CCN1CCCCC1 HWSIZQMXQQXDNZ-UHFFFAOYSA-N 0.000 claims description 3
- 201000006474 Brain Ischemia Diseases 0.000 claims description 3
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 3
- HWHLPVGTWGOCJO-UHFFFAOYSA-N Trihexyphenidyl Chemical group C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 HWHLPVGTWGOCJO-UHFFFAOYSA-N 0.000 claims description 3
- 206010046543 Urinary incontinence Diseases 0.000 claims description 3
- 230000009102 absorption Effects 0.000 claims description 3
- 238000010521 absorption reaction Methods 0.000 claims description 3
- 206010008118 cerebral infarction Diseases 0.000 claims description 3
- 230000004899 motility Effects 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 230000028327 secretion Effects 0.000 claims description 3
- 229960001032 trihexyphenidyl Drugs 0.000 claims description 3
- 208000010877 cognitive disease Diseases 0.000 claims description 2
- 230000006870 function Effects 0.000 claims description 2
- 230000003871 intestinal function Effects 0.000 claims description 2
- WYDUSKDSKCASEF-LJQANCHMSA-N (1s)-1-cyclohexyl-1-phenyl-3-pyrrolidin-1-ylpropan-1-ol Chemical compound C([C@](O)(C1CCCCC1)C=1C=CC=CC=1)CN1CCCC1 WYDUSKDSKCASEF-LJQANCHMSA-N 0.000 claims 3
- 229960005253 procyclidine Drugs 0.000 claims 3
- 230000003925 brain function Effects 0.000 claims 1
- 230000006735 deficit Effects 0.000 claims 1
- 230000004064 dysfunction Effects 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 description 17
- 239000004480 active ingredient Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 208000027089 Parkinsonian disease Diseases 0.000 description 3
- 206010034010 Parkinsonism Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 2
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical class C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- YIJAXVWJZJYWPI-UHFFFAOYSA-N 1-piperidin-1-ylpropan-1-ol Chemical class CCC(O)N1CCCCC1 YIJAXVWJZJYWPI-UHFFFAOYSA-N 0.000 description 1
- YGTUPRIZNBMOFV-UHFFFAOYSA-N 2-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C=C1 YGTUPRIZNBMOFV-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 0 CC1(*)*N(*)CC1 Chemical compound CC1(*)*N(*)CC1 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 206010029333 Neurosis Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical class C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
- 229960005301 pentazocine Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 150000007519 polyprotic acids Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000001177 vas deferen Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Definitions
- the invention relates to the new use of known active substances in the treatment of diseases which are influenced by substances with affinity for sigma receptors.
- British patent 1313781 describes substituted piperidines which are said to have a long-lasting, centrally stimulating effect.
- 1-pyrrolidino and 1-piperidinopropanols and butanols are known from the prior art (for example DE-PS 1005067, DE-PS 871 899, DE-PS 875660, DD-PS 50603 and USP 2,411,664) e.g. Biperiden, Cycrimin, Pridinol, Procyclidin, Trihexyphenidyl, Triperiden or Difenidol, which can partly also be used in the therapy of Parkinsonism.
- the invention relates to the use of compounds of the formula I, wherein either
- R3 is hydrogen or 1-4C-alkyl
- R4 is hydrogen or 1-4C-alkyl
- R5 is hydrogen or 1-4C-alkyl, m is 2 and n is 0, or wherein
- R4 cyclopentyl, cyclohexyl, phenyl, 2-norbornen-5-yl or
- R5 hydroxyl is 1 or 2 and n is 2 or 3, and their salts for the manufacture of medicaments for the treatment of
- 1-4C-Alkyl stands for straight-chain or branched alkyl radicals with 1 to 4 carbon atoms. Examples include the butyl, iso-butyl, sec-butyl, tert-butyl, propyl, isopropyl, ethyl and especially the methyl radical.
- Suitable salts for compounds of the formula I are preferably all pharmacologically acceptable acid addition salts with the inorganic and organic acids customarily used in galenics.
- Water-soluble and water-insoluble acid addition salts with acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2- (4-hydroxybenzoyl) benzoic acid, butyric acid, sulfosalicylic acid, maleic acid, maleic acid are suitable.
- the compounds of the formula I can be optically active compounds.
- the invention therefore includes both the enantiomers and their mixtures and racemates.
- Diseases which are favorably influenced by substances with affinity for sigma receptors include psychoses (schizophrenia), hallucinations in connection with psychotic disorders and chronic psychological depressions, psychoneuroses, brain disorders (cerebral ischemia, cognitive dysfunction), disorders of the intestinal function (absorption , Secretion, motility) and other smooth muscular organs, such as vas deferens and urinary bladder (urinary incontinence), and other diseases such as those associated with affinities for sigma receptors and as described, for example, in the literature reviews of BL Largent et al. (Eur. J. Phar a-col., 155, 345-7, 1988), S.I. Deutsch et al.
- auxiliaries and excipients suitable for the desired pharmaceutical formulations based on his specialist knowledge.
- active ingredient carriers for example antioxidants, dispersants, emulsifiers, defoamers, taste correctives, preservatives, solubilizers, dyes or in particular permeation promoters and complexing agents (e.g. cyclodextrins) can be used.
- the active ingredients can be administered orally, rectally, parenterally or percutaneously.
- the active ingredient (s) when administered orally in a daily dose of about 0.01 to about 20, preferably 0.05 to 5, in particular 0.2 to 2.0 mg / kg body weight ⁇ per weight, optionally in the form of several, preferably 1 to 4 individual doses to achieve the desired result.
- a daily dose of about 0.01 to about 20, preferably 0.05 to 5, in particular 0.2 to 2.0 mg / kg body weight ⁇ per weight, optionally in the form of several, preferably 1 to 4 individual doses to achieve the desired result.
- parenteral treatment similar or (in particular when the active compounds are administered intravenously) generally lower doses can be used. Any person skilled in the art can easily determine the optimum dosage and mode of application of the active ingredients required on the basis of his or her specialist knowledge.
- the pharmaceutical preparations can also contain one or more pharmacologically active constituents of other groups of medicaments.
- the invention further comprises the use of the compounds according to the invention for the treatment of sigma receptor-modulated diseases.
- One embodiment of the invention is the use of compounds from
- R3 is hydrogen or 1-4C-alkyl
- R4 is hydrogen or 1-4C-alkyl
- R5 is hydrogen or 1-4C-alkyl, m is the number 2 and n is the number 0.
- a further embodiment of the invention is the use of compounds of the formula I in which R1 is hydrogen, R2 is hydrogen, R3 is phenyl, R4 is cyclopentyl, cyclohexyl, phenyl, 2-norbornen-5-yl or
- a further embodiment of the invention is the use of compounds of the formula I in which R 1 is phenyl, R 2 phenyl, R 3 is hydrogen, R 4 is methyl, R 5 is methyl, m is the number 2 and n is the number 0, and their salts for the preparation of drugs for the treatment of sigma receptor-modulated diseases.
- a further embodiment of the invention is the use of compounds of the formula I in which R1 is phenyl, R2 is phenyl, R3 is methyl, R4 is methyl, R5 is methyl, m is the number 2 and n is the number 0, and their salts for the preparation ⁇ treatment of drugs for the treatment of sigma receptor-modulated diseases.
- a further embodiment of the invention is the use of compounds of the formula I in which R1 is hydrogen, R2 is hydrogen, R3 is phenyl, R4 is 2-norbornen-5-yl, R5 is hydroxyl, m is 2 and n is 2, and their salts for the production of medicaments for the treatment of sigma receptor-modulated diseases.
- a further embodiment of the invention is the use of compounds of the formula I in which R1 is hydrogen, R2 is hydrogen, R3 is phenyl, R4 is cyclopentyl, R5 is hydroxy, m is 2 and n is 2, and their salts for the preparation of drugs for the treatment of sigma receptor-modulated diseases.
- a further embodiment of the invention is the use of compounds of the formula I in which R1 is hydrogen, R2 is hydrogen, R3 is phenyl, R4 is phenyl, R5 is hydroxyl, the number 2 and n is the number 2, and their salts for the preparation of Medicaments for the treatment of sigma receptor-modulated diseases.
- a further embodiment of the invention is the use of compounds of the formula I in which R1 is hydrogen, R2 is hydrogen, R3 is phenyl, R4 is cyclohexyl, R5 is hydroxy, m is 1 and n is 2, and their salts for the preparation of drugs for the treatment of sigma receptor-modulated diseases.
- a further embodiment of the invention is the use of compounds of the formula I in which R1 is hydrogen, R2 is hydrogen, R3 is phenyl, R4 is cyclohexyl, R5 is hydroxy, m is 2 and n is 2, and their salts for the preparation of drugs for the treatment of sigma receptor-modulated diseases.
- a further embodiment of the invention is the use of compounds of the formula I in which R1 is hydrogen, R2 is hydrogen, R3 is phenyl, R4 is tricyclo [2.2.1.0 ⁇ ] hept-2-yl, R5 is hydroxy, m is the number 2 and n denotes the number 2 and their salts for the production of medicaments for the treatment of sigma-receptor-modulated diseases.
- a further embodiment of the invention is the use of compounds of the formula I in which R1 is hydrogen, R2 is hydrogen, R3 is phenyl, R4 is phenyl, R5 is hydroxy, m is 2 and n is 3, and their salts for the preparation of drugs for the treatment of sigma receptor-modulated diseases.
- Ki values ( ⁇ M) sigma receptors NMDA receptors (pentazocin binding) (MK-801 binding)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention concerne l'utilisation de composés de formule (I), dans laquelle R1, R2, R3, R4, R5, m et n ont les notations données dans la description, pour la fabrication de médicaments destinés au traitement de maladies modulées par un récepteur sigma.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP96911993A EP0819001A1 (fr) | 1995-04-05 | 1996-04-02 | Utilisation de composes de piperidine ou de pyrrolidine substitues pour le traitement de maladies modulees par un recepteur sigma |
| JP8529973A JPH11503140A (ja) | 1995-04-05 | 1996-04-02 | シグマ−受容体が変調した疾患を治療するための、置換されたピペリジン化合物またはピロリジン化合物の使用 |
| AU54993/96A AU5499396A (en) | 1995-04-05 | 1996-04-02 | Use of substituted piperidine or pyrrolidine compounds for t reating sigma-receptor modulated disorders |
| US08/930,642 US5994369A (en) | 1995-04-05 | 1996-04-02 | Substituted piperidine or pyrrolidine compounds for treating sigma-receptor modulated disorders |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH976/95-1 | 1995-04-05 | ||
| CH97695 | 1995-04-05 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1996031208A2 true WO1996031208A2 (fr) | 1996-10-10 |
| WO1996031208A3 WO1996031208A3 (fr) | 1996-11-14 |
Family
ID=4199588
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1996/001442 WO1996031208A2 (fr) | 1995-04-05 | 1996-04-02 | Utilisation de composes de piperidine ou de pyrrolidine substitues pour le traitement de maladies modulees par un recepteur sigma |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US5994369A (fr) |
| EP (1) | EP0819001A1 (fr) |
| JP (1) | JPH11503140A (fr) |
| AU (1) | AU5499396A (fr) |
| WO (1) | WO1996031208A2 (fr) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999004793A2 (fr) * | 1997-07-23 | 1999-02-04 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Budipine s'utilisant dans le traitement d'affections inflammatoires du systeme nerveux |
| WO1999021839A1 (fr) * | 1997-10-27 | 1999-05-06 | Nippon Kayaku Kabushiki Kaisha | Composes heterocycliques et leur utilisation |
| WO1999033453A2 (fr) * | 1997-12-31 | 1999-07-08 | Sepracor Inc. | R-procyclidine utilisee dans le traitement de l'incontinence urinaire |
| WO1999033454A2 (fr) * | 1997-12-31 | 1999-07-08 | Sepracor Inc. | Procyclidine-s aux fins du traitement de l'incontinence urinaire |
| WO2000014066A1 (fr) * | 1998-09-09 | 2000-03-16 | Pfizer Products Inc. | Derives de 4,4-biarylpiperidine possedant une activite de recepteur opioide |
| US7378425B2 (en) | 2002-03-29 | 2008-05-27 | Eisai R & D Management Co., Ltd. | (1-Indanone)-(1,2,3,6-tetrahydropyridine) compounds |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1161240B1 (fr) * | 1998-12-18 | 2005-08-17 | Bristol-Myers Squibb Pharma Company | N-ureidoalkyl-piperidines utilisees en tant que modulateurs de l'activite des recepteurs des chimiokines |
| US6897234B2 (en) * | 1999-12-17 | 2005-05-24 | Bristol-Myers Squibb Pharma Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| WO2005080396A2 (fr) * | 2004-02-25 | 2005-09-01 | Basf Aktiengesellschaft | Composes azolopyrimidine et leur utilisation pour lutter contre des champignons nuisibles |
| WO2009147831A1 (fr) * | 2008-06-04 | 2009-12-10 | 株式会社Celest | Procédé et composition pharmaceutique pour le traitement de troubles mentaux |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995000131A1 (fr) * | 1993-06-23 | 1995-01-05 | Cambridge Neuroscience, Incorporated | Ligands du recepteur sigma et leur utilisation |
-
1996
- 1996-04-02 AU AU54993/96A patent/AU5499396A/en not_active Abandoned
- 1996-04-02 EP EP96911993A patent/EP0819001A1/fr not_active Withdrawn
- 1996-04-02 WO PCT/EP1996/001442 patent/WO1996031208A2/fr not_active Application Discontinuation
- 1996-04-02 JP JP8529973A patent/JPH11503140A/ja active Pending
- 1996-04-02 US US08/930,642 patent/US5994369A/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995000131A1 (fr) * | 1993-06-23 | 1995-01-05 | Cambridge Neuroscience, Incorporated | Ligands du recepteur sigma et leur utilisation |
Non-Patent Citations (5)
| Title |
|---|
| ARCHIVES OF PSYCHIATRY AND NEUROLOGICAL SCIENCES, Bd. 231, Nr. 3, 1982, Seiten 213-220, XP002011683 BECKMANN, H. ET AL: "The cholinolytic Biperiden in depression" * |
| DISEASES OF THE NERVOUS SYSTEM, Bd. 38, Nr. 5, Mai 1977, Seiten 353-355, XP002011682 JELLINEK, T.: "Mood elevating effect of Trihexyphenidyl and Biperiden in individuals taking antipsychotic medication" * |
| LIFE SCI, 1991, 49 (17) P1229-35, ENGLAND, XP002011681 HUDKINS RL ET AL: "M1 muscarinic antagonists interact with sigma recognition sites " * |
| PAEDIATRIC NEUROLOGY, Bd. 11, Nr. 4, November 1994, Seiten 346-348, XP002011685 VOGELS, O.J.M. ET AL: "Focal dystonia and speech impairment responding to anticholinergic therapy" * |
| SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, Bd. 15, Nr. 66, 1980, Seiten 15-26, XP002011684 HEATHCOTE, B.V. ET AL: "Pirenzepine selectively inhibits gastric acid secretion: a comparitive pharmacological study between pirenzepine and seven other antiacetylcholine drugs" * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999004793A2 (fr) * | 1997-07-23 | 1999-02-04 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Budipine s'utilisant dans le traitement d'affections inflammatoires du systeme nerveux |
| WO1999004793A3 (fr) * | 1997-07-23 | 1999-04-08 | Byk Gulden Lomberg Chem Fab | Budipine s'utilisant dans le traitement d'affections inflammatoires du systeme nerveux |
| WO1999021839A1 (fr) * | 1997-10-27 | 1999-05-06 | Nippon Kayaku Kabushiki Kaisha | Composes heterocycliques et leur utilisation |
| WO1999033453A2 (fr) * | 1997-12-31 | 1999-07-08 | Sepracor Inc. | R-procyclidine utilisee dans le traitement de l'incontinence urinaire |
| WO1999033454A2 (fr) * | 1997-12-31 | 1999-07-08 | Sepracor Inc. | Procyclidine-s aux fins du traitement de l'incontinence urinaire |
| WO1999033453A3 (fr) * | 1997-12-31 | 1999-10-07 | Sepracor Inc | R-procyclidine utilisee dans le traitement de l'incontinence urinaire |
| WO1999033454A3 (fr) * | 1997-12-31 | 1999-10-21 | Sepracor Inc | Procyclidine-s aux fins du traitement de l'incontinence urinaire |
| US6130242A (en) * | 1997-12-31 | 2000-10-10 | Sepracor Inc. | S-procyclidine for treating urinary incontinence |
| WO2000014066A1 (fr) * | 1998-09-09 | 2000-03-16 | Pfizer Products Inc. | Derives de 4,4-biarylpiperidine possedant une activite de recepteur opioide |
| US6720336B2 (en) | 1998-09-09 | 2004-04-13 | Pfizer, Inc. | 4,4-biarylpiperidine derivatives |
| US7378425B2 (en) | 2002-03-29 | 2008-05-27 | Eisai R & D Management Co., Ltd. | (1-Indanone)-(1,2,3,6-tetrahydropyridine) compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| AU5499396A (en) | 1996-10-23 |
| JPH11503140A (ja) | 1999-03-23 |
| EP0819001A1 (fr) | 1998-01-21 |
| US5994369A (en) | 1999-11-30 |
| WO1996031208A3 (fr) | 1996-11-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69231395T3 (de) | Neue medizinische Indikation für Tachykinin-Antagonisten | |
| DE69612465T2 (de) | Verwendung von Rifamyciderivaten zur Behandlung von Chlamydia-Infektionen | |
| DE602004007840T2 (de) | Pyrazolopyrimidinon und ihre Verwendung als PDE-Inhibitoren | |
| DE3855325T2 (de) | Oxothiolane und Derivate, diese enthaltende pharmazeutische Zubereitungen und ihre Verwendung als Arzneimittel | |
| DE69729099T2 (de) | Amine zur herstellung von medikamenten zur hemmung der tumorzellenvermehrung | |
| EP0819001A1 (fr) | Utilisation de composes de piperidine ou de pyrrolidine substitues pour le traitement de maladies modulees par un recepteur sigma | |
| EP1051170B1 (fr) | Utilisation d'aminomethyl-chromanes pour empecher la degenerescence neuronale et favoriser la regeneration neuronale | |
| DE69825605T2 (de) | Behandlung der schizophrenie und der psychose | |
| DE4430091A1 (de) | Verwendung von N-substituierten Phenothiazinen | |
| DE60028538T2 (de) | Kondensierte heterocyclische verbindungen und ihre verwendung zur behandlung von neurodegenerativen erkrankungen | |
| DE2802864A1 (de) | 3-isobutoxy-2-pyrrolidino-n-phenyl- n-benzylpropylamin, verfahren zu seiner herstellung und es enthaltende arzneimittel | |
| DE3853931T2 (de) | Optische Isomere von einem Spirochinuclidinderivat. | |
| Rippstein et al. | Influence of the Lewis Acidity of the Tin Atom on the Magnitude of the Intramolecular Sn* N Interaction in 2-(Me 2 NCH 2) C 6 H 4 Sn (X) RR′ | |
| DE69104054T2 (de) | Melatoninderivat mit therapeutischer aktivität, das in der dermatologie anwendbar ist. | |
| DE69127285T2 (de) | Verwendung von verbindungen zur behandlung von altersbedingtem gedächtnisschwund und anderen kognitiven störungen | |
| DE2724478C2 (de) | 5,11-Dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-on-derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE3873210T2 (de) | Verwendung von benzylpyridin-derivaten zur herstellung eines arzneimittels zur behandlung der demenz. | |
| DE69320030T2 (de) | Benzisoxazol-derivate und diese enthaltende pharmazeutische zusammensetzungen | |
| DE2314335A1 (de) | Neue amide der apovincaminsaeure, deren salze, herstellung und medikamente, die diese enthalten | |
| DE60307049T2 (de) | Verwendung von Piperazin- Phenothiazin- Derivaten zur Herstellung eines Arzneimittels mit neuroprotektiven und/oder neurotropischen Wirkungen auf das ZNS und/oder PNS | |
| DE69129623T2 (de) | Behandlungsverfahren für therapiewiderstehende schizophrenie mit amperozide | |
| DE68915595T2 (de) | Verwendung von Isoxazolinonen als cerebro-aktive Medikamente. | |
| CH630058A5 (de) | Verfahren zur herstellung von neuen disubstituierten phenolaethern des 3-amino-2-hydroxypropans. | |
| KR102688072B1 (ko) | 신규한 화합물, 이의 제조방법 및 이를 함유하는 신경 손상, 신경 질환, 또는 발달 장애에 대한 신경세포의 증식 촉진, 분화, 및/또는 재생을 통한 치료 또는 예방용 약제학적 조성물 | |
| DE2324634A1 (de) | Cycloalkyllactamimide, verfahren zu ihrer herstellung und diese verbindungen enthaltende therapeutische zubereitungen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A2 Designated state(s): AU BG BY CA CN CZ EE HU JP KR LT LV MX NO NZ PL RO RU SG SI SK UA US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
| AK | Designated states |
Kind code of ref document: A3 Designated state(s): AU BG BY CA CN CZ EE HU JP KR LT LV MX NO NZ PL RO RU SG SI SK UA US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A3 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 1996911993 Country of ref document: EP |
|
| ENP | Entry into the national phase |
Ref country code: JP Ref document number: 1996 529973 Kind code of ref document: A Format of ref document f/p: F |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 08930642 Country of ref document: US |
|
| WWP | Wipo information: published in national office |
Ref document number: 1996911993 Country of ref document: EP |
|
| NENP | Non-entry into the national phase |
Ref country code: CA |
|
| WWW | Wipo information: withdrawn in national office |
Ref document number: 1996911993 Country of ref document: EP |